[Antibiotic resistance here to stay? Compensatory mutations restore virulence of resistant bacteria]

Abstract

Bacterial antibiotic resistance has increased alarmingly because of overuse of antibiotics both in humans and animals. One way of reversing this development is to reduce the use of antibiotics, thus promoting the disappearance of the resistant bacteria already present in humans and the environment. This approach is based on the assumption that resistance is conferred at the cost of impaired survival fitness in the absence of antibiotics, as compared with sensitive strains. It seems to be generally true that resistant bacteria are less fit than the respective sensitive strains, which suggests that resistance may be reversible. However, a complicating factor is the frequent finding in resistant strains of various types of compensatory mutations that restore fitness without concomitant loss of resistance. Thus, second-site compensatory mutations may allow resistant strains to persist and compete successfully with sensitive strains even in an environment depleted of antibiotics. It is concluded in the article that, if compensatory mutations are as common in clinical settings as they are in the laboratory, many types of resistance will be irreversible.